线粒体功能改变在孕期骨铅动员致大鼠肾损伤中的机制研究OA

[Background]Lead is a typical persistent environmental pollutant that can accumulate in bones for decades.During pregnancy,alterations in calcium metabolism promote the mobilization of bone lead,resulting in secondary exposure;however,the mechanisms by which pregnancy-asso-ciated bone lead mobilization affects maternal renal function remain unclear. [Objective]To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. [Methods]Newly weaned female Wistar rats were randomly assigned to a control or a lead-ex-posed group administered either 0.05%sodium acetate or 0.05%lead acetate in drinking water.Following a 4-week lead exposure and a 4-week washout period,the females were co-housed with healthy age-matched males for mating.Rats were sacrificed at early(gestational day 3)and late(gestational day 17)pregnancys-tages,respectively.Renal histopathology was assessed using hematoxylin and eosin staining staining.Mitochondria-related indicators,in-cluding oxidative stress,inflammatory responses,and energy metabolism,were measured.Differential metabolites were identified using serum metabolomics. [Results]Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner,characterized by degeneration of proximal tubular epithelial cells,glomerular hyaline changes,and interstitial inflammatory cell infiltration.Repeated measures ANOVA indicated a significant interaction between the treatment factor(lead exposure)and the temporal factor(gestational stage)on renal injury(P<0.001).Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde(MDA)and reactive oxygen species(ROS)(P<0.05),accompanied by a reduction in superoxide dismutase(SOD)and reduced glutathione(GSH)activities(P<0.05);regarding inflammatory markers,levels of interleukin-18(IL-18)and interleukin-1β(IL-1β)were elevated(P<0.01),whereas interleukin-33(IL-33)was decreased in the lead-exposed group(P<0.05);energy metabolism-related indicators,including adenosine triphosphate(ATP)level,Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities,and mitochondrial respiratory chain complexes I,III,and V activities,were significantly reduced(P<0.05)in the lead-exposed gorup.The typical differential metabolite N-methylisoleucine,identified through serum metabolomics analysis,was negatively correlated with blood lead levels,kidney injury scores,and IL-1β,while positively correlated with catalase(CAT)activity and Ca2+-Mg2+-ATPase. [Conclusions]Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.